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| 25mg |
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| Targets |
Aldosterone synthase[1]; Baxdrostat is a selective aldosterone synthase (CYP11B2) inhibitor.
Baxdrostat selectively targets aldosterone synthase (cytochrome P450 11B2, mitochondrial; CYP11B2). It exhibits a high selectivity ratio for CYP11B2 over the highly homologous enzyme 11β-hydroxylase (CYP11B1, responsible for cortisol synthesis), with a selectivity factor (SFCYP11B1 IC50/CYP11B2 IC50) of 100. The binding affinity (Ki) of Baxdrostat for human CYP11B2 is 13 nM. For monkey CYP11B2, the Ki is 4 nM. |
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| ln Vitro |
In cellular enzyme assays using G-402 cells transfected with human CYP11B2, Baxdrostat demonstrated potent inhibitory activity with an EC50 of 14 nM. The compound competitively inhibits aldosterone synthase, blocking the conversion of 11-deoxycorticosterone to aldosterone. In vitro studies confirmed that Baxdrostat exhibits a high selectivity ratio for aldosterone synthase compared to 11β-hydroxylase (CYP11B1), with a selectivity factor of approximately 100-fold. The primary metabolite of Baxdrostat, CIN-107-M, also exhibits selectivity for aldosterone synthase over 11β-hydroxylase, with its two enantiomers showing >20-fold greater selectivity for aldosterone synthase.
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| ln Vivo |
In a Phase 2 trial (BrigHTN) involving patients with treatment-resistant hypertension, Baxdrostat (2 mg once daily) significantly reduced blood pressure. The mean seated systolic blood pressure (SBP) reduction from baseline was 15.7 mmHg, with a placebo-adjusted reduction of 9.8 mmHg at 12 weeks. The 1 mg dose achieved a placebo-adjusted SBP reduction of 8.7 mmHg. In a Phase 3 trial (BaxHTN), these results were confirmed, with approximately 40% of patients achieving healthy blood pressure levels (<130 mmHg) compared to fewer than 20% on placebo. In non-human primate studies, Baxdrostat blunted aldosterone production while having no effect on cortisol levels. The drug also demonstrated dose-dependent reductions in plasma aldosterone and mild decreases in plasma sodium levels with increases in potassium levels.
In healthy volunteers, baxdrostat showed dose-dependent reductions in plasma aldosterone levels (up to ~70% at 3 mg/day) without affecting cortisol levels, confirming its selectivity for CYP11B2 over CYP11B1 (cortisol synthase) [1] In patients with resistant hypertension, baxdrostat (1 mg, 2 mg, or 10 mg daily) significantly reduced systolic blood pressure (placebo-adjusted reductions up to 11.0 mmHg at 10 mg) [2] |
| Enzyme Assay |
The inhibitory activity of Baxdrostat on human CYP11B2 and CYP11B1 was assessed using a cellular enzyme assay. G-402 cells were transfected with expression plasmids containing the open reading frame (ORF) for either human CYP11B1 or CYP11B2 under the control of a CMV promoter, along with a neomycin resistance marker. Transfected cells were selected and maintained in McCoy's 5a Medium Modified containing 10% fetal calf serum and 400 μg/ml G418 (Geneticin) at 37°C under 5% CO2/95% air. For the assay, cells were plated in 96-well plates and incubated for 16 hours in DMEM/F12 medium containing 2.5% charcoal-treated fetal calf serum and appropriate substrate concentrations (0.3-10 μM 11-deoxycorticosterone for CYP11B2 or 11-deoxycortisol for CYP11B1). After incubation, supernatant aliquots were transferred and analyzed for product concentration (aldosterone for CYP11B2; cortisol for CYP11B1) using homogeneous time-resolved fluorescence (HTRF) assays.
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| Cell Assay |
The cellular activity of Baxdrostat was evaluated using G-402 cells stably expressing human CYP11B2. These cells were maintained in McCoy's 5a Medium Modified containing 10% fetal calf serum and 400 μg/ml G418 at 37°C under an atmosphere of 5% CO2/95% air. For the cellular enzyme assay, cells were plated onto 96-well plates and incubated for 16 hours in DMEM/F12 medium containing 2.5% charcoal-treated fetal calf serum and 0.3-10 μM of the substrate 11-deoxycorticosterone. Following incubation, an aliquot of the supernatant was transferred, and the concentration of the expected product, aldosterone, was determined using HTRF assays.
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| Animal Protocol |
Initial pharmacology characterization studies were performed in cynomolgus monkeys, where Baxdrostat was shown to blunt aldosterone production while having no effect on cortisol levels.
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| ADME/Pharmacokinetics |
phase I study in healthy volunteers showed that basilatin had linear pharmacokinetic characteristics in the 0.5–10 mg dose range, with a median time to peak (Tmax) of 2–4 hours and a mean half-life of approximately 15–20 hours [1]. A crossover study showed no significant pharmacokinetic interaction between basilatin and metformin [3].
Baxdrostat is rapidly absorbed following oral administration, with peak plasma concentrations (Tmax) observed within 4 hours after dosing. The drug exhibits a mean plasma half-life (t1/2) ranging from approximately 26 to 31 hours, which supports once-daily dosing. Plasma exposures increase in a dose-proportional manner over the therapeutic dose range. At steady state (day 10 of once-daily dosing), Baxdrostat exposure is approximately 2- to 2.5-fold higher than after a single dose. Approximately 7% of the dose is recovered unchanged in urine on day 1, increasing to about 32% at steady state on day 10. The primary metabolite, CIN-107-M, represents 8-11% of the parent compound based on Cmax and 10-22% based on AUC, but is not considered to contribute substantially to the pharmacologic effect. Baxdrostat exhibits high oral bioavailability and rapid absorption. |
| Toxicity/Toxicokinetics |
Baxdrostat was well tolerated in healthy volunteers and patients with refractory hypertension, with no serious adverse events reported. Mild hyperkalemia was observed in some patients. [1][2][br>]
In a Phase 1 multiple ascending dose study in healthy volunteers, Baxdrostat was safe and well-tolerated. There were no deaths or serious adverse events reported. All treatment-emergent adverse events in subjects receiving Baxdrostat were mild in severity. Common mild adverse events included headache, nasopharyngitis, and diarrhea. Baxdrostat had no meaningful impact on plasma cortisol levels, demonstrating its selectivity for aldosterone synthase. The drug resulted in mild dose-dependent decreases in plasma sodium levels and increases in potassium levels.
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| References |
[1]. Results from a phase 1, randomized, double-blind, multiple ascending dose study characterizing the pharmacokinetics and demonstrating the safety and selectivity of the aldosterone synthase inhibitor baxdrostat in healthy volunteers. Hypertens Res. 2023 Jan;46(1):108-118.
[2]. The selective aldosterone synthase inhibitor Baxdrostat significantly lowers blood pressure in patients with resistant hypertension. Front Endocrinol (Lausanne). 2022 Dec 9;13:1097968. [3]. Results From a Randomized, Open-Label, Crossover Study Evaluating the Effect of the Aldosterone Synthase Inhibitor Baxdrostat on the Pharmacokinetics of Metformin in Healthy Human Subjects. Am J Cardiovasc Drugs. 2023 May;23(3):277-286. |
| Additional Infomation |
Baxdrostat is an investigational drug for the treatment of refractory hypertension. Its mechanism of action is through targeting excessive aldosterone production. Its selectivity for CYP11B2 avoids the risk of cortisol deficiency [1][2].
Baxdrostat (also known as CIN-107, RO6836191) is a novel tetrahydroisoquinoline derivative being developed by AstraZeneca (acquired via the purchase of CinCor Pharma in 2023 for approximately $1.8 billion). The drug is designed to address disorders associated with elevated aldosterone, a key driver of hypertension, cardiovascular disease, and renal dysfunction. Unlike traditional mineralocorticoid receptor blockers (e.g., spironolactone) which can cause endocrine side effects due to cortisol dysregulation, Baxdrostat's high selectivity for CYP11B2 over CYP11B1 allows it to lower aldosterone without affecting cortisol, potentially offering a superior safety profile. The Phase 3 BaxHTN trial results presented at the European Society of Cardiology (ESC) Congress 2025 and published in the New England Journal of Medicine showed that adding Baxdrostat (1 mg or 2 mg once daily) to background antihypertensive therapy led to clinically meaningful SBP reductions (approximately 9-10 mmHg vs. placebo) that persisted up to 32 weeks with no unanticipated safety findings. The drug is also being evaluated for primary aldosteronism and in combination with dapagliflozin for chronic kidney disease with hypertension. |
| Molecular Formula |
C22H25N3O2
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|---|---|
| Molecular Weight |
363.45
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| Exact Mass |
363.194
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| Elemental Analysis |
C, 72.70; H, 6.93; N, 11.56; O, 8.80
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| CAS # |
1428652-17-8
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| Related CAS # |
(S)-Baxdrostat;1428652-16-7;(Rac)-Baxdrostat;1428652-15-6
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| PubChem CID |
71535962
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
2.2
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
27
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| Complexity |
566
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C(N[C@H]1C2=C(CCC1)C(C1C=CC3=C(C=1)CCC(=O)N3C)=CN=C2)(=O)CC
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| InChi Key |
VDEUDSRUMNAXJG-LJQANCHMSA-N
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| InChi Code |
InChI=1S/C22H25N3O2/c1-3-21(26)24-19-6-4-5-16-17(12-23-13-18(16)19)14-7-9-20-15(11-14)8-10-22(27)25(20)2/h7,9,11-13,19H,3-6,8,10H2,1-2H3,(H,24,26)/t19-/m1/s1
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| Chemical Name |
N-[(8R)-4-(1-methyl-2-oxo-3,4-dihydroquinolin-6-yl)-5,6,7,8-tetrahydroisoquinolin-8-yl]propanamide
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| Synonyms |
CIN-107; CIN107; Baxdrostat; Baxdrostat [INN]; NF3P9Z8J5Y; RO6836191; CIN 107
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: 100 mg/mL (275.14 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.72 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (5.72 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7514 mL | 13.7571 mL | 27.5141 mL | |
| 5 mM | 0.5503 mL | 2.7514 mL | 5.5028 mL | |
| 10 mM | 0.2751 mL | 1.3757 mL | 2.7514 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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